tbuckley/cabot-search huggingface dataset:
PD1 inhibition effect on immunization with MRNA vaccines against SARS-CoV-2.
Authors: Martin Majer, Justin Knoefler, Elizabeth Fauchier Little, Megan Powell, Edward J. Ordorica, Roxanna Arakozie, Phuc Tran, Duke Ha, Socheat Cheam, Linda Lay, Andrew Le, Min Park, Gurbir Atwal, Hanh Nguyen, Mee Yang, Sudeep Kaur Ghuman, Sarah Jones, Narinder Singh, Roy Shannon
Journal: Journal of Clinical Oncology (2022)

e14594 Background: We provide care for the rural, low-income, and underserved population of Oroville. The community has a vaccination rate of 50% and booster rate of over 20% in the 3 rd year of the ongoing global SARS-CoV-2 pandemic in 2022. During this period, a subset of our cancer patients benefited from the use of immune checkpoint inhibitors. Methods: This is a cross-sectional observational study of the effectiveness of a mRNA-based vaccine in medical care workers compared to patients with systemic malignancies treated with immunomodulation of PD-1 and CTLA-4 inhibitors. The study was approved by the hospital IRB. We evaluated the total anti-Spike protein antibody titer using a commercial semi-quantitative assay, Labcorp Test #164090. All subjects received 3 doses of the mRNA vaccine. We excluded anyone who was administered therapeutic monoclonal antibodies (mAb) or had a recent infection within 120 days. Results: Subjects with systemic malignancies were significantly older, p = 0.0001 by t-test: median age: 76, range: 64-82, compared to health care workers: median age: 52, range: 21-75. Accrual had to be prematurely stopped upon the arrival of Omicron wave in the community. Out of the seven subjects treated with immunomodulation, six received nivolumab, including two in combination with ipilimumab. One subject received pembrolizumab. Six of the subjects had metastatic disease: one was treated adjuvantly for locally advanced esophageal adenocarcinoma. The rest had NSCLC and one case of urothelioma. We divided the groups to those who had the highest titer of antibody versus everybody else and found a similar distribution in both groups using the Chi 2 test. The vast majority of the healthcare workers, 24/27 or 89%, had above the upper limit antibody titer. Patients with systemic malignancy, 5/7 or 71%, had above the upper limit antibody titer p = N.S. Conclusions: Three doses of the mRNA vaccine provided high titers irrespective of frailty or age. We hypothesize that immunomodulation could favorably affect vaccination response.
Tracking of tumor-derived exosomal PD-L1 for cancer diagnosis and surveilance of immunotherapy response by dual-aptamer-encoded nanocatalyst assembly.
Authors: Tianyu Zeng, Hai Shi, Chunxiao Sun, Fan Yang, Wei Li, Yan Liang, Ziyi Fu, Yongmei Yin
Journal: Journal of Clinical Oncology (2022)

e14528 Background: Immunohistochemistry is still the gold standard for identifying suitable populations for ICB therapy by staining PD-L1 in tumor tissue. However, IHC may be frustrated by intratumoral heterogeneity, subject to sampling error, and risk damaging tissue. Application of tumor-derived exosomal PD-L1 (Exo-PD-L1) for searching suitable populations for immunotherapy and monitoring immunotherapy response in breast cancer is often hindered by normal cells-derived Exo-PD-L1and the limitation of existed tools. Methods: We have developed a dual-target-specific aptamer recognition activated in situ hybridization chain reaction (HCR)-weaved nanocatalyst assembly (TRACE) on exosome for visualized tracking of Exo- PD-L1 . Leveraging theexcellent selectivity of dual-aptamer recognition, high sensitivity of HCR-encoded nanocatalyst assembly, and high accessibility of color changes-based analysis. The clinical significance of tumor-derived Exo- PD-L1 were evaluated in a small cohort of clinical samples (4 healthy donors (HDs), 20 PD-L1-negative (PD-L1-N) breast cancer patients, and 10 PD-L1-positive (PD-L1-P) breast cancer patients) by using this TRACE system. All serum is collected and CT is scanned at approximately every 2 cycles. Results: The TRACE system can accurately distinguish PD-L1-positive breast cancer patients from healthy donors and PD-L1-negative patients by selectively and sensitively detecting tumor-derived Exo-PD-L1, with the most appropriate cutoff value of 0.6168 and 0.3603, respectively. The receiver operating characteristic (ROC) curve demonstrates the excellent accuracy (AUC: 1) of this TRACE system due to the high sensitivity and specificity. Moreover, the TRACE system provide a quantified and visualized tool for dynamically revealing immunotherapy response based on the levels of tumor-derived Exo-PD-L1, including stable, progressive, and partial response. Conclusions: The TRACE system may have a great potential for supplementing the existing standards and assisting to screen appropriate patients for ICB therapy and explore situable patients from different therapeutic regimenin-depth. As a companion diagnostics tool, the TRACE system may also rise great hope for improving the management of dosage, therapeutic regimen, and efficacy evaluation by providing timely feedback of immunotherapy response.
Spatial meta-transcriptomics reveal intratumor bacterial association with lung cancer cells showing a distinct oncogenic signature.
Authors: Chen Zhao, Abigail Wong-Rolle, Qiang Dong, Yunhua Zhu, Prajan Divakar, Jyh Liang Hor, Noemi Kedei, Madeline Wong, Desiree Tillo, Elizabeth A. Conner, Arun Rajan, David S. Schrump, Chengcheng Jin, Ronald N. Germain
Journal: Journal of Clinical Oncology (2022)

8531 Background: The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors is missing, information needed to improve treatment outcomes and prognosis. Methods: To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and three microbe targets (16S rRNA, 28S rRNA and CMV). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in tumor samples from 12 patients with early-stage lung cancer. Results: Bacterial burden was significantly higher in tumor cells compared to T cells, macrophages, other immune cells, and stroma. This burden increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that lung intratumor bacteria derive from the latter route of entry. Expression of oncogenic β-catenin and epithelial-mesenchymal transition pathway genes was strongly correlated with bacterial burden, as were tumor subtypes, mutation profile, histology and smoking history. Conclusions: Intratumor bacteria were enriched with tumor cells and associated with multiple oncogenic pathways, supporting a rationale for reducing the local intratumor microbiome in lung cancer to optimize clinical outcomes. This research was supported in part by the Intramural Research Programs of the NCI and NIAID. Other funding sources included ASCO Young Investigator Award, SITC-AstraZeneca Immunotherapy in Lung Cancer (Early Stage NSCLC) Clinical Fellowship Award, NIH Bench-to-Bedside and Back Program (BtB), NCI R00 award (CA226400), Emerson Collective Cancer Research fund, Lung Cancer Research Foundation (LCRF) pilot grant and W.W. Smith Trust Foundation award. This study was approved by NCI institutional review board (NCT00242723 and NCT02146170) and Animal Use and Care Committee at the University of Pennsylvania (#806875).
Financial impact of immunotherapy-related adverse events among inpatient admissions with solid malignancies.
Authors: Rayli Pichardo, Yazan Abu Omar, Ding Wang
Journal: Journal of Clinical Oncology (2022)

e18825 Background: Immune checkpoint inhibitors (ICPis) have shifted the landscape of cancer treatment from conventional cytotoxic regimens. The mechanism of action involves suppression of immunologic checkpoints that often results on a unique spectrum of side effects associated with immune-mediated inflammations. The Aim of this study is to evaluate the financial impact from immune-related adverse events (IrAEs) reflected in hospitalized patients undergoing anti-neoplastic immunotherapy using the data from a nation-wide database. Methods: We performed retrospective analysis with the National Inpatient Sample (NIS) using ICD10-CM and PCS codes to identify patients with solid tumors hospitalized for immunotherapy between October 2015 and 2018. Inpatient data from patients with or without having developed IrAEs during the hospitalizations were compared in this study. IRAEs included systemic symptoms, diarrhea/colitis, hepatic and endocrine adverse events. Baseline characteristics and inpatient complication variables were collected and analyzed between these two groups. Results: From 5,795 admissions of ICPi-treated cancer patients, 1,160 patients or 20 % of these hospitalizations presented with IrAEs, females represented (37.5%) with an age of 57 years though not statistically different from admissions without IrAE. On the other hand, length of stay was statistically longer (7 vs 5 days, p &lt; 0.05) with higher admission expenses ($184,255 vs $ 133,305, p &lt; 0.05) from IRAE-associated admissions. Higher IrAEs were observed among patients who were ICPi-treated for genitourinary (GU) cancers (22% vs 15%, p &lt; 0.05). IRAE as an independent risk factor was associated with higher costs even when adjusted for other risk factors, significantly contributed to a higher admission expenses by a coefficient at $46,624 (SE +/- $13,943). Conclusions: Although ICPi-therapies have offered various clinical benefits among cancer patients. They have also contributed to both direct and indirect costs of cancer management. Our analysis showed a higher IrAE incidence associated with ICPi-treated GU cancer patients, patients who developed IRAEs had a longer hospital stay and higher in-hospital mortality, resulting in higher care expenses as one of the indirect financial burdens of ICPi therapies, no differences were observed between gender, race, or income.[Table: see text]
Outcomes of second-line therapies in patients with metastatic de novo small cell prostate cancer (SCPC) and treatment-emergent neuroendocrine prostate cancer (tNEPC).
Authors: Corbin Eule, Junxiao Hu, Sulaiman Al-Saadi, Katharine Collier, Patrick James Boland, Rana R. McKay, Vivek Narayan, Dominick Bosse, Amir Mortazavi, Tracy L Rose, Elaine T. Lam
Journal: Journal of Clinical Oncology (2022)

e17022 Background: De novo SCPC and tNEPC in metastatic castrate resistant prostate cancer (mCRPC) are rare, aggressive cancers with a poor prognosis. After first-line (1L) platinum chemotherapy (PLT), there is no consensus on 2L treatments. This multi-institutional, retrospective study examines practice patterns among clinicians and evaluates the outcomes of patients (pts) with SCPC or tNEPC in the 2L setting. Methods: After IRB approval, pts with a pathologic diagnosis of SCPC or tNEPC (any % of SC or NE histology defined by institutional review) were identified. Pts diagnosed between 2000-2020 who received 1L PLT and any 2L systemic therapy (tx) for SCPC or tNEPC were included. Standardized data collection templates containing demographic, clinical, and pathologic variables were collected. The primary endpoint was objective response rate (ORR) to 2L tx. Secondary endpoints included PSA response, time on 2L treatment, and overall survival (OS) from time of 2L tx. Data was analyzed using descriptive statistics. Results: Forty-two pts (21 SCPC, 21 tNEPC) from 6 institutions were included. At SCPC/tNEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 60.5, 68.0) and median PSA of 3.0 ng/dL (IQR 0.5, 21.8). The most common sites of metastasis included lymph node (78.6%), bone (54.8%), and liver (52.4%). For 1L tx, 37 pts (88.1%) received PLT and 5 (11.9%) had PLT + immunotherapy (IMM). For treatment to the prostate, 21 (51.2%) had none, 7 (17.1%) radiation (RT), 9 (22.0%) surgery, 3 (7.3%) RT + surgery, and 1 (2.4%) brachytherapy alone. Concurrent ADT was given to 32 pts (76.2%) in the 1L and 2L. At last follow-up, 34 pts (81.0%) were dead, 4 (9.5%) were alive, and 4 (9.5%) were lost to follow-up/censored. For 2L tx, 10 pts (23.8%) received PLT, 8 (19.0%) taxane monotherapy (TAX), 10 (23.8%) IMM, 8 (19.0%) other chemotherapy (CHX), and 6 (14.3%) other tx. Among 38 pts evaluable for response, the ORR was 15.8% (6 pts with PR: 4 PLT, 1 IMM, 1 CHX). PSA response ≥ 50% to 2L tx was seen in 5 of 29 pts with PSA data (17.2%). Other outcomes data are reported in Table. Conclusions: In this retrospective study, pts with SCPC or tNEPC who reached 2L tx received a wide variety of treatment regimens, reflecting the lack of consensus in this tx setting. ORR was low and overall prognosis was poor in the 2L regardless of tx choice. Pts on 2L immunotherapy seemed to have the shortest mOS. [Table: see text]
Characteristics of germline DNA damage response gene mutations in ovarian cancer in Southwest China.
Authors: Rutie Yin, Jinghong Chen, Qingli Li, Xinyu Yan, Jie Wang, Kemin Li, Liang Song, Lan Zhong, Yu Ma, Mengpei Zhang, Jing Zeng, Danqing Wang, Shida Zhu
Journal: Journal of Clinical Oncology (2022)

e17606 Background: DNA damage response (DDR) pathway is responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cell genome. Germline mutations of DDR genes are potentially predictive and prognostic biomarkers for oncotherapy and may predispose carries to some malignancies. We aimed to profile the characteristics of germline DDR gene mutations in ovarian cancer treated in our center to provide highlight on regional disparity and susceptibility genes. Methods: We retrospectively and unselectively enrolled a cohort of patients diagnosed as advanced epithelial ovarian cancer from October 2016 to October 2020, who had complete clinicopathological data and signed informed consent for gene testing. In total, peripheral blood samples from 432 patients were collected in our center and evaluated on specific germline alterations. This study was approved by the Medical Ethics Committee of West China Second University Hospital, Sichuan University (Ethical Lot Number 20200076). Results: The most observed mutated genes were FANCD2 (47%), BRCA1 (27%), BRCA2 (27%), ERCC5 (18%) and RECQL4 (17%). The frequency of missense mutation was higher than other mutation types in most genes, except FANCD2, TSC2 and PHOX2B. Deleterious DDR gene mutations and deleterious homologous recombination repair gene mutations were detected in 346 patients (80.1%) and 240 patients (55.6%), respectively. The most observed genes with deleterious mutation were BRCA1 (18.5%), BRCA2 (12.5%), ERCC5 (6%), MLH1 (5.8%), PALB2 (3.7%) and ERCC4 (3.7%). The prevalence of BRCA2 deleterious mutations is higher than other studies (patients mainly from Eastern China), and so are the mismatch repair genes. Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. Conclusions: Our study presented here showed the germline DDR gene mutation spectrum of ovarian cancer patients in Southwest China, which is different from other regions of China in some genes. And we found germline FANCD2 and RECQL4 deleterious mutations were likely ovarian cancer susceptibility sites, which should draw more attention in patient management and genetic counseling.
Enhancing accrual to clinical trials of minority patients with gynecologic malignancy.
Authors: Olivia Lara, Bhavana Pothuri
Journal: Journal of Clinical Oncology (2022)

e13535 Background: Central to improving survival of patients with gynecologic malignancy is participation in therapeutic, surgical and preventative clinical trials. Minority population accrual is particularly poor representing a disparity in cancer care. We sought to evaluate enrollment of minority populations at an urban NCI-designated Comprehensive Cancer Center before and after the NCI call to action June 2020. Methods: Data on patient enrollment in gynecologic oncology clinical trials (14 therapeutic and 4 non-therapeutic) was obtained from Perlmutter NCI-designated Comprehensive Cancer Center. Primary outcomes were the proportion of newly accrued patients by race participating in trials between January 2019 to September 2021. Results: Over the entire study period 154 total patients were enrolled in therapeutic and non-therapeutic clinical trials. Enrollment by cancer type included 100 (71.4%) ovarian, 16 (7.1%) uterine, 12 (7.9%) cervical and 26 (13.5%) solid tumor trials. White patients comprised 69% (69 of 100) of patients on ovarian cancer trials. Uterine cancer trials by race consisted of 50 % White, 37.5% Black, 6.2% Asian and 6.2% Other race patients. Eighty-eight patients were enrolled into clinical trial prior to the NCI alert. By race these patients were: White, 65.9% (58 of 88); Black, 3.4% (3 of 88); Asian, 11.4% (10 of 88) and Other race, 19.3% (17 of 88). Hispanic patients comprised 13.6% (12 of 88) of the population. Following the call to action an additional 66 patients were enrolled in clinical trial. This included 42 (63.6%) White, 14 (21.2%) Black, 5 (7.57%) Asian, 5 (7.6%) Other race and 8 (12.12%) Hispanic patients. The percentage of Black patients enrolled in clinical trial increased four -fold over the time period (3.4% vs 21.2%, p &lt; 0.05). Conclusions: Overall during this time period we found an increase in number of Black patients accrued to clinical trial. This indicates disparities in clinical trial enrollment can be modified by institutional awareness. The role of patient education, financial and logistical barriers and language discordance to minority participation in clinical trials should be studied further.
Role of cytoreductive surgery for the second ovarian cancer relapse in patients previously treated with chemotherapy alone at first relapse: A subanalysis of the DESKTOP III trial.
Authors: Jalid Sehouli, Christina Fotopoulou, Ignace Vergote, Alexander Reuss, Gwenael Ferron, Werner Meier, Stefano Greggi, Berit J. Mosgaard, Frederic Selle, Frederic Guyon, Christophe Pomel, Fabrice Lecuru, Rongyu Zang, Kristina Hellmann, Jae-Weon Kim, Margarita Romeo, Francesco Raspagliesi, Brynhildur Eyjólfsdóttir, Andreas Du Bois, Philipp Harter
Journal: Journal of Clinical Oncology (2022)

5520 Background: The DESKTOP III trial has demonstrated a significant survival benefit in AGO-score positive patients who underwent complete cytoreduction at 1st relapse compared to those treated with chemotherapy alone. The question whether eligible patients who missed the opportunity of potentially life prolonging surgery at 1st relapse would benefit from surgery at the time of their second relapse, remains open. Methods: Patients randomized in the standard, non-surgical arm of the DESKTOP III trial who underwent cytoreductive surgery at a subsequent relapse at investigator’s discretion were separately analyzed. Results: The median progression-free survival (PFS) counted from randomization of 201 patients in the control arm of DESKTOP III was 14.0 months. 171 (85%) had progressive or relapsing disease and 32 of 171 (19%) underwent cytoreductive surgery. Patients’ median age at this subsequent surgery was 63 years (range: 46 – 78). Complete tumor resection was achieved in 19 patients (60%), while 5 (16%) had postoperative residual disease (n = 8 missing data). Sixteen patients (50%) commenced systemic treatment within 90 days from surgery, as documented. Thirty- and 90-day surgical mortality rates were 1 (3%) and 2 (6%), respectively. Within a postoperative median follow-up time of 43.8 months, 12 (38%) deaths were reported. Median overall survival after surgery (OS) was 54.0 months. One- and 2-year OS rates were 91% and 84%, respectively. Conclusions: Cytoreductive surgery for subsequent ovarian cancer relapse appears feasible and with low mortality in selected patients who received non-surgical treatment at 1st relapse despite a positive AGO-score. Surgery should be considered as an option in carefully selected patients also later in their journey within a specialized gynecological cancer setting. Clinical trial information: NCT01166737.
Augmented alpha-beta PSMA radioligand therapy in metastatic prostate cancer: Analysis of prognostic factors for survival.
Authors: Harshad Kulkarni, Jaya Khushalani, Brandon Robert Mancini, Kevin Maupin, Franz Christoph Robiller, Richard Baum, Frankis Almaguel
Journal: Journal of Clinical Oncology (2022)

e17025 Background: PSMA-targeted radioligand therapy (PRLT) using the alpha-emitter Ac-225 PSMA-617 is effective in metastatic prostate cancer progressing after beta-emitter-based PRLT using Lu-177 PSMA-617, and in the presence of diffuse bone marrow metastases. Xerostomia is a dose-limiting factor in PRLT using Ac-225. Augmented Alpha-Beta PRLT is a concept of concomitantly administering Lu-177 and Ac-225 PSMA in lower activities, as a trade-off between efficacy and the dose-limiting toxicity, i.e., xerostomia. The objective of this study was to compare overall survival (OS), progression-free survival (PFS), and incidence of xerostomia among metastatic prostate cancer patients who received Ac-225 PSMA-617 augmentation in the initial phase of Lu-177 PSMA-617 RLT compared to those who received it in the late phase. Initial phase is defined as first two cycles of PSMA radioligand therapy (PRLT) vs late phase as after two cycles. We also examined prognostic factors associated with OS and PFS. Methods: Kaplan Meier method was used to examine survival curves and log-rank tests were conducted to examine differences in survival by groups. Cox Proportional Hazard (CPH) model was used to examine the impact of bone marrow and visceral metastasis and age on OS and PFS. Progression was defined as an increase of ≥ 25% in prostate-specific antigen (PSA) levels. Results: 68 patients who received Ac-225 PSMA-617 by itself, or Ac-225 PSMA-617 augmentation to Lu-PSMA-617 were included in the analysis. Out of these, 15 received early augmentation, 50 received late augmentation, and 3 received Ac-225 PSMA-617 alone. Of these, 48 experienced cancer progression and 21 died due to cancer progression. Median OS was 47 months and PFS was 11 months. Those who received early augmentation had significantly better PFS (median PFS not reached during study period) compared to those who received late augmentation (median PFS: 9 months) (p = 0.02). Early augmentation was associated with lower likelihood of xerostomia (p = 0.09). CPH model suggested that visceral or bone marrow metastasis were associated with significantly worse prognosis for PFS (p = 0.04). Conclusions: In patients progressing after Lu-177 PSMA radioligand therapy and those with diffuse bone-marrow metastases, an earlier augmentation with Ac-225 PSMA-617 is associated with better PFS and lower side effects such as xerostomia. Having visceral or bone marrow metastasis is a poor prognostic indicator for PFS in augmented alpha-beta PSMA radioligand therapy.